State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
School of Basic Medical Sciences, Jiujiang University, Jiujiang 332005, China.
Mol Pharm. 2020 May 4;17(5):1586-1595. doi: 10.1021/acs.molpharmaceut.9b01296. Epub 2020 Mar 30.
It is a challenging task to suppress the bitterness of liquid preparations, especially for children. Bitter molecules are highly dispersible in liquids, leading to a strong and instant stimulation of the bitter receptors. At present, there is no effective way to correct this issue except for adding sweeteners, resulting in an unsatisfying taste. Based on the three-point contact theory, which is a universally accepted mechanism of bitterness formation, a new idea and application of amphiphilic block copolymers (ABCs) for bitterness suppression was proposed for the first time. We found that ABCs could widely inhibit the bitterness of four typical bitter substances. The mechanism is that ABCs self-assemble to form association colloids, which attract bitter components and reduce their distribution in the molecular form in solution. The bitter components were demonstrated to automatically embed in the spiral hydrophobic cavity of the hydrophobic chain of the ABCs, and their special interaction dispersed the positive electrostatic potential of bitter groups. The combination did not affect the pharmacokinetic parameters and pharmacodynamics of bitter drugs. These findings highlight the novel application of ABCs for the inhibition of bitterness and illuminate the underlying inhibition mechanisms.
抑制液体制剂的苦味是一项极具挑战性的任务，特别是对于儿童而言。苦味分子在液体中高度分散，会即刻强烈刺激苦味受体。目前，除了添加甜味剂之外，还没有其他有效方法来纠正这一问题，这导致药物的口感并不令人满意。基于苦味形成的普遍公认机制——三点接触理论，我们首次提出了一种用于抑制苦味的两亲嵌段共聚物（ABC）的新理念和应用。我们发现 ABC 可以广泛抑制四种典型苦味物质的苦味。其作用机制是 ABC 自组装形成缔合胶体，吸引苦味成分并减少其在溶液中以分子形式的分布。研究表明，苦味成分自动嵌入 ABC 疏水链的螺旋疏水性腔内，其特殊的相互作用会分散苦味基团的正静电势。这种结合并不影响苦味药物的药代动力学参数和药效。这些发现突出了 ABC 在抑制苦味方面的新颖应用，并阐明了其潜在的抑制机制。
